Functional analysis of the novel RING-finger domain containing Fanconi anemia protein

2016 Fiscal Year Final Research Report

• Project/Area Number: 26281021
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto University
• Principal Investigator: Ishiai Masamichi 京都大学, 放射線生物研究センター, 准教授 (90298844)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: DNA修復 / ユビキチン / ファンコニ貧血 / 相同組換え / RPA / RAD51 / RFWD3 / FANCW

Outline of Final Research Achievements

Fanconi anemia (FA) is a hereditary disorder defective in DNA interstrand crosslinks (ICL) and characterized by developmental anomalies, progressive bone marrow failure, leukemia, and solid tumors.
RFWD3 is a recently identified FA protein FANCW whose ubiquitin E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. We identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51, in vitro and in vivo. From further analysis, our data reveal a mechanism that facilitates timely removal of RPA and RAD51 from DNA damage sites, which is crucial for progression to the late-phase HR.

Free Research Field

分子生物学